This program will be concerned with several aspects of energy metabolism during embryonic and fetal development. A major effort will be investigation of energy pathways in fetal and newborn animals. Substrate preferences for a variety of fetal tissues will be studied as will fatty acid oxidation and synthesis and the enzymes involved in those pathways. Investigations of fetal biochemistry will include measurement of fatty acid activating enzymes and transferases as well as determination of metabolic intermediates, free coenzyme A, and carnitine and coenzyme A esters of fatty acids. A major thrust of the program will be concerned with the effects of inhibitors and hormones on fetal metabolic and morphological differentiation. Thyroxin and chloramphenicol will be of particular interest as they are known to affect energy systems of the cell. These studies will hopefully provide models with which to investigate the influence of hormones on normal development and the effects of inhibitors on the production of malformations. Several sources of fetal material will be utilized in this investigation, ie., bovine fetuses, chick embryos, rat and guinea pig fetuses and tissue culture of heart and skeletal muscle. Norms for biochemical and morphological differentiation of muscle cells in culture will be established and a variety of hormones and pharmacological agents will be screened for their effects on this or similar tissue culture systems. This project has been funded and is currently underway at the Massachusetts General Hospital, Boston, Mass. At this time I am requesting transfer of the award for the final year of support to Yale University School of Medicine.